Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0SC8W5)

DOT Name Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B)
Synonyms EC 3.1.3.36; 75 kDa inositol polyphosphate-5-phosphatase; Phosphoinositide 5-phosphatase; 5PTase
Gene Name INPP5B
Related Disease
Adult glioblastoma ( )
Dent disease type 2 ( )
Glioblastoma multiforme ( )
Hypothyroidism ( )
Joubert syndrome ( )
Muscular dystrophy ( )
Oculocerebrorenal syndrome ( )
Amyotrophic lateral sclerosis ( )
Cataract ( )
Glaucoma/ocular hypertension ( )
UniProt ID
I5P2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3MTC; 3N9V; 4CML; 5A7I; 5A7J
EC Number
3.1.3.36
Pfam ID
PF16776 ; PF21310 ; PF00620
Sequence
MDQSVAIQETLAEGEYCVIAVQGVLCEGDSRQSRLLGLVRYRLEHGGQEHALFLYTHRRM
AITGDDVSLDQIVPVSRDFTLEEVSPDGELYILGSDVTVQLDTAELSLVFQLPFGSQTRM
FLHEVARACPGFDSATRDPEFLWLSRYRCAELELEMPTPRGCNSALVTWPGYATIGGGRY
PSRKKRWGLEEARPQGAGSVLFWGGAMEKTGFRLMERAHGGGFVWGRSARDGRRDEELEE
AGREMSAAAGSRERNTAGGSNFDGLRPNGKGVPMDQSSRGQDKPESLQPRQNKSKSEITD
MVRSSTITVSDKAHILSMQKFGLRDTIVKSHLLQKEEDYTYIQNFRFFAGTYNVNGQSPK
ECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVK
LIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSH
LAAHIEEYERRNQDYKDICSRMQFCQPDPSLPPLTISNHDVILWLGDLNYRIEELDVEKV
KKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAP
AWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVRVVNDELYRKTLEEIVRSLD
KMENANIPSVSLSKREFCFQNVKYMQLKVESFTIHNGQVPCHFEFINKPDEESYCKQWLN
ANPSRGFLLPDSDVEIDLELFVNKMTATKLNSGEDKIEDILVLHLDRGKDYFLSVSGNYL
PSCFGSPIHTLCYMREPILDLPLETISELTLMPVWTGDDGSQLDSPMEIPKELWMMVDYL
YRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICY
STYHNCLECSGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFG
SLLLRNPAGHQKLDMTEKKKAQEFIHQFLCNPL
Function Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.
Tissue Specificity Platelets.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Reactome Pathway
Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204 )
Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183 )
BioCyc Pathway
MetaCyc:HS05898-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Altered Expression [1]
Dent disease type 2 DISJFNHL Strong Genetic Variation [2]
Glioblastoma multiforme DISK8246 Strong Altered Expression [1]
Hypothyroidism DISR0H6D Strong Genetic Variation [3]
Joubert syndrome DIS7P5CO Strong Biomarker [4]
Muscular dystrophy DISJD6P7 Strong Genetic Variation [5]
Oculocerebrorenal syndrome DIS8TEDY Strong Biomarker [6]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [7]
Cataract DISUD7SL Limited Biomarker [8]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [8]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B). [12]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B). [13]
------------------------------------------------------------------------------------
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Type II inositol 1,4,5-trisphosphate 5-phosphatase (INPP5B). [11]
------------------------------------------------------------------------------------

References

1 Lipid phosphatases SKIP and SHIP2 regulate fibronectin-dependent cell migration in glioblastoma.FEBS J. 2019 Mar;286(6):1120-1135. doi: 10.1111/febs.14769. Epub 2019 Feb 16.
2 Digenic mutations of human OCRL paralogs in Dent's disease type 2 associated with Chiari I malformation.Hum Genome Var. 2016 Dec 8;3:16042. doi: 10.1038/hgv.2016.42. eCollection 2016.
3 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
4 Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E.J Cell Sci. 2017 Feb 1;130(3):563-576. doi: 10.1242/jcs.197004. Epub 2016 Dec 7.
5 Mutations in INPP5K, Encoding a Phosphoinositide 5-Phosphatase, Cause Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment. Am J Hum Genet. 2017 Mar 2;100(3):523-536. doi: 10.1016/j.ajhg.2017.01.024. Epub 2017 Feb 9.
6 Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy.J Am Soc Nephrol. 2017 May;28(5):1399-1407. doi: 10.1681/ASN.2016080913. Epub 2016 Nov 28.
7 FIG4 variants in central European patients with amyotrophic lateral sclerosis: a whole-exome and targeted sequencing study.Eur J Hum Genet. 2017 Feb;25(3):324-331. doi: 10.1038/ejhg.2016.186. Epub 2017 Jan 4.
8 Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe.PLoS One. 2013 Jun 21;8(6):e66727. doi: 10.1371/journal.pone.0066727. Print 2013.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
11 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
12 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
13 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.